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Biomedical subjects

S Ikeda

Publications and source records attributed to S Ikeda.

At least 397 records · Page 22Linked to original sources

Synthesis and structure-activity relationships of thienylcyanoguanidine derivatives as potassium channel openers.

In our series of studies on potassium channel openers, several thienylcyanoguanidine derivatives were synthesized and evaluated for smooth muscle relaxation activity in vitro. Among the newly synthesized compounds, N-cyano-N'-(5-cyano-3-thienyl)-N"-tert-pentylguanidine (4b) and N-(5-bromo-3-thienyl)-N'-cyano-N"-tert-pentylguanidine (4f) exhibited excellent activity which was proved to be based on potassium channel-opening action. Bioisosterism between benzene and thiophene ring was observed in the arylcyanoguanidines. After intravenous administration to dogs, 4b lowered the blood pressure more strongly than pinacidil.

Animals↗

Expression of LH-alpha and -beta subunit mRNAs in the rat placenta.

Gonadotropic activity is present in the placenta of various mammals including humans. Human and equine chorionic gonadotropin (CG) are well characterized and known to be glycoprotein hormones, as are pituitary LH, TSH and FSH. In the rat, however, the placental gonadotropin molecule has not been identified, and in fact the existence of CG in the rodent is still controversial. In the present study, the placental expression of mRNA for CG-like molecules was investigated by PCR with mixed primers designed for the CG-beta subunit based on the amino acid sequences common to the rat LH-beta, human LH-beta, equine LH-beta and human CG-beta subunits and for the alpha subunit designed from the rat LH-alpha subunit. PCR with mRNA extracted from the placenta (day 10 of pregnancy) amplified several bands including cDNA identical to part of rat LH-alpha and -beta. Furthermore, expression of these genes was confirmed in the placenta on days 10, 12, 14, 16, 18 and 20 of pregnancy by PCR with another set of primers specific to rat LH-alpha and -beta and by Southern hybridization with 32P-labeled cDNAs for LH-alpha and -beta. The specific bands for these subunit mRNAs were amplified in the placenta, as well as in the positive control i.e. the anterior pituitary gland, but were not detected in other tissues including decidual tissue, liver, spleen, intestine, brain and kidney. Expression of the mRNAs was observed in both the junctional and labyrinth zones of the placental tissue. The rat choriocarcinoma cell line Rcho-1 also expressed LH-alpha but not LH-beta regardless of the stage of differentiation in vitro. Here we show the expression of LH-alpha and -beta mRNAs in the rat placenta.

Amino Acid Sequence↗

A 55-kDa endonuclease of mammalian mitochondria: comparison of its subcellular localization and endonucleolytic properties with those of endonuclease G.

A novel endonuclease of 55-kDa was found in rat liver mitochondria by a zymographic assay, in addition to the 29 kDa enzyme that is well-known as endonuclease G (Endo G). Subcellular localization of these enzymes in rat liver cells was examined by biochemical fractionation. Endo G was located in both nuclei and mitochondria as has been previously reported, while the 55-kDa enzyme was only detected in the mitochondrial fraction. The levels of the endonucleases in the mitochondria varied greatly among the rat organs, and the activity in the heart was about 30 times higher than that in the liver. The 55-kDa enzyme and Endo G were extracted from bovine heart mitochondria with 0.4 M NaCl. During purification the 55-kDa enzyme and Endo G were copurified because of their similar chromatographic behavior, so they were separated by gel filtration or electrophoresis in the presence of SDS and the proteins were then renatured. The nucleolytic properties of the 55-kDa enzyme resembled those of Endo G and other known mitochondrial nucleases. The enzyme degraded single-stranded DNA more rapidly than duplex DNA at a weak alkaline pH1 requiring Mg2+ or Mn2+ but not Ca2+ or Zn2+. Nicks generated by the enzyme had 5'-P and 3'-OH ends. The 55-kDa enzyme, like Endo G, displayed an unusually strong preference to nick within a (dG)n.(dC)n tract.

Animals↗

Japan's aging population. Implications for healthcare.

In the early years of the next century, the Japanese population may well become the oldest in the world. The Japanese government's concentration on post-World War II economic expansion meant that the government only fully woke up to the financial implications of having a large elderly population when oil prices were raised in the 1970s, highlighting Japan's economic dependence on global markets. This article explains the process by which policy regarding Japan's elderly developed both before and after these oil price increases. The measures of healthcare cost containment that the government introduced in response to the increased financial pressure are described, with a particular focus on pharmaceuticals. This article shows that the government has achieved a degree of success in terms of containing pharmaceutical costs, but that future effects on the quality of healthcare are uncertain. Ultimately, a wider application of a per diem fee in place of the prevalent fee-for-service system, and the realisation of plans to improve the social service infrastructure, would be the best path for policy to follow.

Aging↗

Transient hypertension due to adrenal hemorrhage in a patient with von Recklinghausen's disease.

A 29-year-old man with von Recklinghausen's disease suddenly developed severe epigastric pain and was admitted to hospital. Physical examination revealed elevated blood pressure (200/130 mmHg) and tachycardia (162 bpm). Initially, he was suspected to have appendicitis, and appendectomy was performed immediately; however, appendicitis was not demonstrable pathologically. Retroperitoneal hematoma was found incidentally during the operation. Further clinical and laboratory examination demonstrated a marked increase in the urinary excretion of catecholamines. There was no evidence of pheochromocytoma on computed tomography or magnetic resonance imaging; however, these imaging studies simply showed a hematoma at the right adrenal gland. Transient hypertension and tachycardia, resembling pheochromocytoma, was caused by adrenal hemorrhage.

Adrenal Gland Diseases↗

[Squamous cell carcinoma and basal cell carcinoma].

Both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are very common in skin malignancy. Operative therapy is the first choice at the treatment for SCC and BCC in early stage. After excision for large skin tumor, occasionally we use skin flap or musculocutaneous flap or free flap. At the old patient of Stage III and IV SCC and BCC, sometimes reduction surgery is useful at the combination therapy. Radiation as adjuvant therapy is sometimes useful for not only SCC but also BCC. The clinical efficacy of CA (C' A') chemotherapy (CDDP, ADM or CBDCA, EPI-ADM), was evaluated on Stage III, IV SCC and BCC. The response rate was 63% in SCC and 75% in BCC.

Adult↗

[Bropirimine (U-54461S) early phase II clinical studies--to investigate the efficacy and safety of bropirimine treatment on various malignant tumors (urological, hematologic, and dermal cancers)].

Early Phase II clinical studies with bropirimine (U-54461S) having interferon (IFN) inducing and direct antiproliferative activities were conducted in patients with various solid tumors or hematologic neoplasm at 34 institutions nationwide. To investigate the safety and efficacy of the treatment, bropirimine was orally administered to the patients at the dose of 1g every two hours, three times a day for three consecutive days with a four day drug-free interval. Among the 65 patients registered, 60 patients were eligible and 44 patients completed bropirimine treatment in accordance with the respective protocols. Complete response (CR) was observed in 7 cases, and partial response (PR) was observed in 4 cases, so the efficacy rate was 25.0% (7 CRs + 4 PRs/44). Classified by target tumors, the efficacy rates were 12.9% (6 CRs/14) in bladder CIS, 33.3% 1 CR/3) in superficial bladder cancer. 11.1% 1 PR/9) in renal cell carcinoma, and 42.9% (3 PRs/7) in malignant lymphoma, respectively. Adverse drug reactions frequently observed were influenza-like symptoms such as fever (60.0%) and generalized malaise (21.7%), gastrointestinal symptoms like anorexia (56.7%) and nausea/vomiting (43.3%), and adverse effects on the circulatory system such as tachycardia (15.0%) and abnormalities in ECG (11.7%). Most of these symptoms were relieved or improved. Abnormalities in laboratory tests observed frequently were adverse effects on the liver such as elevations in GPT (33.3%), in GOT (31.7%), and in LDH (18.3%) or on the blood system like a decrease in RBC (18.3%), leukopenia (26.7%), or neutropenia (25.0%). In conclusion, bropirimine treatment proved to be effective for bladder CIS in particular, suggesting that it will be promising for use in the treatment of the disease.

Adult↗

Comparison of adenosine triphosphate and dipyridamole in diagnosis by thallium-201 myocardial scintigraphy.

UNLABELLED: We examined whether 201Tl myocardial scintigraphy with intravenous infusion of adenosine triphosphate (ATP) can be substituted for dipyridamole (DIP) in the diagnosis of coronary artery disease CAD). METHODS: The coronary flow reserve (CFR) during intravenous infusion of ATP (0.10-0.20 mg/kg/min) was compared with that during intravenous infusion of DIP (0.56 mg/kg) using a Doppler flow wire in 19 subjects with normal coronary arteries. The highest CFR level was found in the ATP dose range of 0.16-0.20 mg/kg/min. The CFR at the ATP dose of 0.16 mg/kg/min was significantly higher than that during DIP infusion (4.2 versus 3.6) (p < 0.01), for which reason we adopted this dose of ATP. According, 201Tl SPECT in 140 patients with suspected CAD was performed after infusion of 0.16 mg/kg/min of ATP in 70 of them and 0.56 mg/kg of DIP in the 70 others. RESULTS: ATP stress 201Tl SPECT showed no significant difference in sensitivity and accuracy from DIP stress 201Tl SPECT (87.0% versus 82.9, and 87.1% versus 78.6, respectively). Adverse effects occurred at higher frequency when ATP was used, but they were mild and disappeared rapidly after administration was stopped. CONCLUSION: ATP stress 201Tl SPECT is accurate and safe. The optimal ATP regimen for this purpose is considered to be a 5-min infusion at 0.16 mg/kg/min. However, our data in CAD patients suggest that ATP stress 201Tl SPECT is equivalent to DIP stress 201Tl SPECT in the detection of CAD.

Adenosine Triphosphate↗

[Skull base aspergillosis granuloma originating from the sphenoid sinus: a case report].

A case of skull base Aspergillus granuloma originating from the sphenoid sinus was reported. This 64-year-old man complained of unilateral visual loss and serious facial pain, and was admitted to our department. He had been treated by transnasal sphenoidectomy because of sphenoid sinus aspergillosis. MRI showed a mass lesion located in the sphenoid sinus, cavernous sinus, ethmoid sinus and intraorbit. Angiography showed severe stenosis of the left internal carotid artery at the cavernous portion. As the symptoms gradually aggravated, we felt compelled to perform intracranial surgical treatment using the extradural approach to the skull base lesions. As the fibrous lesion was very hard and strongly adherent to the surrounding tissues, only partial removal of the lesion and resection of the trigeninal nerve were carried out. After surgery, the patient was released from severe facial pain and had an uneventful course. But, two months later, he died due to Aspergillus meningoencephalitis. Aspergillosis originating from the sphenoid sinus is rare, but it is known that some lesions show abrupt invasive extension to the skull base and the prognosis is bad. Early diagnosis and suitable treatment for the skull base or intracranial lesions is required.

Aspergillosis↗

[Glutathione levels in human colon cancer cell line M7609 following culture in a low sulfur amino acid medium and its sensitivity to various anticancer drugs].

Glutathione levels in human colon cancer cell line M7609 and its sensitivity to anticancer drugs were investigated in a complete medium RPMI-1640 (medium A) and an incomplete medium (medium B), which was prepared by removing glutathione and sulfur amino acids from medium A. Four different medium conditions were prepared by combining a medium A and a medium B; a medium of 100% medium A (Control), a 50:50 mixture medium of medium A and medium B (Condition 2), a 20:80 mixture medium of medium A and medium B (Condition 3), and a 10:90 mixture medium of medium A and medium B (Condition 4). The cells were cultured in each medium for 14 days, and intracellular levels of glutathione were determined to estimate the cell sensitivity to anticancer drugs. There were no significant differences in glutathione levels among the cancer agents in condition 2, as compared to those in the control. In condition 3, the reduced glutathione levels were decreased to 23.1%, where CDDP, ADM, MMC and melphalane showed 2.5, 2.2, 1.8 and 1.5 times greater antitumor activity than in the control, respectively. In condition 4, cell proliferation was too low to collect adequate cells for glutathione determination. These results demonstrated that the decrease in cellular glutathione concentration with this method might enhance the cytotoxic effects of anticancer drugs.

Amino Acids, Sulfur↗

Laparoscopic diagnosis of appendicovesical fistula in a pediatric patient.

Appendicovesical fistula is a rare complication of acute appendicitis in children that is difficult to diagnose preoperatively. A 21-month-old boy with signs and symptoms of recurrent urinary tract infections underwent abdominal ultrasonography, computed tomography (CT), barium enema examination, and cystography, none of which was sufficient to establish a diagnosis; an appendicovesical fistula was demonstrated by laparoscopy. The patient underwent open appendectomy, with resection of the fistula through a small incision, and has recovered without complications.

Appendectomy↗

[Mitral prosthetic valve replaced twice due to repeated prosthetic valve endocarditis: a case report].

A 38-year-old man was admitted to our hospital for detailed examination of fever, cough and yellow sputum. At the age of 32, be had mitral prosthesis for the first time, because of mitral regurgitation due to mitral valve prolapse. Four years previously, he had again undergone mitral prosthetic valve replacement due to prosthetic valve endocarditis due to staphylococcus epidemidis. This occasion, staphylococcus aureus was isolated by arterial blood culture. Transesophageal echocardiography detected vegetation attached to the mitral prosthetic valve and paravalvular leakage. The diagnosis was prosthetic valve endocarditis. He underwent a third mitral prosthetic valve replacement. Detection of the source of infection was difficult only by transthoracic echocardiography, and immediate transesophageal echocardiography seemed mandatory to diagnose bacterial endocarditis.

Adult↗

[Acute acalculous cholecystitis as a complication of cerebrovascular disease].

Acute acalculous cholecystitis (AAC) is a potentially life-threatening complication, which is sometimes found in patients with multiple injuries, burns, or after an operation. It is unclear, however, whether AAC occurs after cerebrovascular disease (CVD). We studied the incidence of AAC complicating CVD and the clinical characteristics of AAC that occurs after CVD. One thousand three patients with CVD were studied who had been admitted at the acute stage to Kenwakai Hospital from January 1989 through September 1995 and to Seguchi Hospital of Neurosurgery from January 1993 through September 1995. There were 557 patients with cerebral infarction, 273 with cerebral hemorrhage, 94 with subarachnoid hemorrhage, and 79 with TIA/RIND. Twelve patients developed acute cholecystitis, ten of whom had AAC. Of the ten patients with AAC, six had cerebral infarction, two cerebral hemorrhage, and two TIA/RIND. Eight of ten were male. The incidence of AAC was 1.0% in the CVD patients studied. The majority of the AAC patients showed severe hemiparesis. The time interval from CVD to the onset of AAC ranged from 1 to 89 days, with a mean of 25.1 days. AAC occurred 0 to 16 days (mean 5.8 days) after the start of oral or tube food intake in five patients. The most common initial symptom was fever (70%), whereas abdominal pain was infrequent (20%). All the patients showed elevated CRPs and abnormal ultrasonographic findings for the gallbladder and some also had leukocytosis (60%) and elevated aminotransferase of more than 100 IU/l (30%). Cholecystectomy was performed on four AAC patients, but five were successfully treated with antibiotics. The cause of AAC complicating CVD seems to be multifactorial and probably is related to fasting, increased bile concentration, and arteriosclerosis. Our results strongly suggest that AAC is an unrecognized but important complication during acute stage CVD patients.

Acute Disease↗

[Study of preoperative combination therapy with UFT + CDDP in patients with gastric and colorectal cancer--concomitant effects based on the thymidylate synthase inhibitory rat].

UNLABELLED: The subjects were 39 patients with gastric cancer and 44 patients with colorectal cancer divided into a group administered 400 mg/day of UFT orally for 2 weeks preoperatively (UFT group) and a group administered 400 mg/day of UFT as well as 40 mg/m2 (i.v.) of cisplatin (CDDP) by drip infusion once concomitantly (UFT + CDDP group). The thymidylate synthase (TS) inhibitory rate was measured in resected specimens and lymph nodes, and the concomitant effects of UFT and CDDP were investigated. RESULTS: 1) The TS inhibitory rate in tumor tissue showed no significant difference between the two groups. 2) The TS inhibitory rate of metastasized lymph nodes was higher in UFT + CDDP group than in the UFT group in gastric cancer patients (p < 0.05). The TS inhibitory rate by lymph node metastasis in patients with gastric cancer or colorectal cancer was significantly higher in metastasized lymph nodes than in non-metastasized lymph nodes in the UFT + CDDP group (p < 0.05 for gastric cancer, p < 0.05 for colorectal cancer). These results indicated that concomitant use of UFT and CDDP appeared to be more effective against metastasized lymph nodes, especially in cases of gastric cancer, than against the primary tumor focus.

Administration, Oral↗

[TNM classification of malignant melanoma and non-melanoma skin cancer].

We abide by a rule of the UICC system of cutaneous malignant melanoma and non-melanoma skin cancer. Assignment of pT stage for melanoma requires accurate measurement of pathological findings. On the other hand, T classification of SCC is decided only by measurement of size. We introduced the UICC TNM staging systems and compared the 5-year survival rate of our cases with the statistical data of the Japanese Society for Skin Cancer.

Basal Cell Carcinoma↗